[Influence of the antagonist of adenosine A1 receptors, 8-cyclopentyl-1 ,3-dipropylxanthine, upon the anticonvulsant activity of antiepileptic drugs in mice].

BACKGROUND

Methylxanthine derivatives (theophylline, caffeine), nonselective antagonists of adenosine receptors, impair the anticonvulsant activity of antiepileptic drugs in experimental models of epilepsy.

THE AIM OF THE STUDY: To answer a question whether the selective antagonist of adenosine A1 receptors, 8-cyclopentyl-1,3-dipropylxanthine (CPX), shares this negative propensity of methylxanthines upon the protective activity of antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate) against maximal electroshock-induced seizures in mice.

RESULTS

Acute CPX (up to 10 mg/kg) did not affect the electroconvulsive threshold but administered chronically for two weeks, it significantly lowered the threshold at 2.5 and 5 mg/kg. CPX (2.5 mg/kg) given acutely reduced only the protection offered by phenobarbital whilst injected chronically in the same dose, it did not only decrease the anticonvulsant action of carbamazepine. Acute CPX did not affect the brain concentration of phenobarbital but, interestingly, the selective adenosine A1 antagonist given chronically elevated the brain concentrations of phenobarbital and valproate, being only ineffective upon that of phenytoin.

CONCLUSIONS

When given chronically, CPX is somewhat similar to theophylline and caffeine, however, these non-selective xanthine derivatives reduced the protective activity of all conventional antiepileptic drugs. Acute CPX expressed weaker negative effects when compared to theophylline or caffeine.